The present disclosure relates to a micro-fluidic chip for use in collection of micro-particles such as cells and micro-beads, a micro-particle sorting device on which the micro-fluidic chip is mounted, and a method of controlling a flow in the micro-fluidic chip. More particularly, the present disclosure relates to a technology for separating and collecting desired micro-particles from a solution in which a plurality of kinds of micro-particles are mixedly present.
In recent years, micro-fluidic chips have been developed in which fine channels and zones for chemical and biological analysis are fabricated in a substrate formed from an inorganic material such as silicon and glass or a polymer material such as plastic, by application of the micro-fabrication technology used in semiconductor industries. Such micro-fluidic chips enable measurement using small amounts of samples, can be manufactured at low cost, and are suited to disposable use. Therefore, these micro-fluidic chips have begun to be utilized in various fields, such as flow cytometry, electrochemical detectors in liquid chromatography, small electrochemical sensors in medicare sites, etc.
In addition, a technology for sorting and collecting micro-particles such as cells and micro-beads, based on the results of analysis in an analysis zone, has also been proposed (see Japanese Patent Laid-Open No. 2003-107099 as referred to as Patent Document 1 hereinafter. Japanese Patent Laid-Open No. 2006-220423 as referred to as Patent Document 2 hereinafter, Japanese Patent Laid-Open No. 2004-85323 as referred to as Patent Document 3 hereinafter, Japanese Patent Laid-Open No. 2003-344260 as referred to as Patent. Document 4 hereinafter). For example, in the micro-fluidic chip described in Patent Document 1, an alternating electric field is generated in the vicinity of an entrance to a sorting channel for sorting and collecting micro-particles, and the micro-particles are sorted by a repulsive dielectric migrating force. Besides, in a cell sorter chip described in Patent Document 2, a gel electrode having an electrolyte-containing gel is provided at such a position as to make contact with a liquid containing micro-particles, and the micro-particles are sorted by utilizing an electrophoretic force.
On the other hand, in a cell analyzing and separating apparatus described in Patent Document 3, micro-particles are separated by guiding them into predetermined branch channels through utilizing an ultrasound or an electrostatic force. Further, Patent Document 4 discloses a method of controlling the moving direction of micro-particles, wherein a branch channel the penetration of the micro-particles into which is to be inhibited is irradiated with laser light, and a shock wave is generated in a liquid.
However, the above-mentioned micro-fluidic chips according to the related art have the following problems. In the separating and collecting methods of the related art as described in Patent. Documents 1 to 4, the micro-particles are to be moved in a direction different from the direction of flow of the liquid containing the micro-particles, and, for this purpose, a strong active force has to be applied to the micro-particles. Therefore, the micro-particles to be collected are liable to be damaged. Particularly, where the micro-particles are biomaterial such as cells, the cells or the like to be collected may be killed.
In addition, in the method described in Patent Documents 1 to 4, the moving direction of micro-particles contained in a liquid flowing continuously in a channel is changed. Under the influence of this change in the moving direction, the flow on the upstream side is disturbed, whereby the accuracy of analysis and the accuracy of collection of the micro-particles are lowered. Further, where a method of controlling the moving direction of micro-particles by an electric field or a magnetic field is applied, the micro-fluidic chip is complicated in configuration.
Furthermore, in the “Jet in Air” system used in flow cytometry according to the related art, micro-particles such as cells are sorted and collected in the atmospheric air, so that an aerosol containing the micro-particles is liable to be generated. Therefore, there is a possibility of mutual contamination of the micro-particles, or the possibility of infection of the measuring operator with an infection disease due to the bio-hazard materials (micro-particles) contained in the aerosol.
Thus, there is a need for a micro-fluidic chip, a micro-particle sorting device and a flow controlling method which cause little damage to micro-particles and by which the moving direction of micro-particles in an enclosed micro-fluidic chip channel can be controlled speedily, accurately and safely.